Sensory receptors are able to detect and discriminate relevant stimuli from backgrounds that vary in stimulus quality and quantity. Studies of these events revealed that sensory adaptation is as fundamentally important to receptor cell output as activation. Indeed, the progression from stimulus reception to termination of receptor cell response is governed by the kinetics of transduction (activation) and adaptation (inactivation). In recent years, investigations utilizing contemporary path clamp electrophysiological and biochemical techniques have substantially advanced our understanding of the mechanisms of olfactory receptor cell activation but the mechanisms of inactivation are largely unknown. The proposed research will utilize these proven techniques to critically examine the mechanisms of olfactory adaptation. In other sensory systems, voltage and Ca+2-activated conductances, electrogenic pump activity, receptor desensitization and changes in ion composition, have been implicated in adaptation. Two types of adaptation, one the result of changes in the background odor environment (background adaptation), the other the previous response history of an cell (receptor cell fatigue), are proposed to influence the cell's current potential to respond. Background adaptation is proposed to act with slower kinetics on odor-activated conductances. Receptor cell fatigue is proposed to act with faster kinetics on the somatic voltage and Ca+2-activated conductances encoding the action potentials. The proposed research will examine the involvement of odor, voltage and Ca+2-activated conductances, as well as, electrogenic pump activity and receptor desensitization, in adaptation. Because adaptation occurs in the olfactory receptor cell, tissue which is exposed to the external environment, the cellular mechanisms of adaptation may be particularly vulnerable to the effects of toxic substances and infection. Indeed, olfactory deficits are correlated with several neurological disorders (Doty et al., 1988). Consequently, knowledge of the cellular machinery of adaptation pathways may aid in elucidating the etiologies of not only olfactory, but possibly other neurological disorders.